The general problem with which we are concerned is the elucidation of cellular mechanisms of gene regulation which relate to the neoplastic process in humans. The phenomenon of ectopic protein synthesis in human cancer offers a good experimental model for investigating this problem. The ectopic synthesis of placental proteins by non-trophoblastic neoplasms is of special interest because of the frequent association of similar characteristics in neoplastic cells and embryonic cells. This has suggested that there may be a link between the mechanisms associated with the depression of the genes synthesizing embryonic proteins and those involved in neoplastic transformation. We are conducting experiments in two fundamental categories. (1) Proof of ectopia: These studies are designed to test the assumption that the placental proteins are indeed synthesized by non-trophoblastic tumors and the assumption that they are coded for by the same genes as their normal counterparts. Chemical structure of the ectopic and placental proteins are being compared by several methods to determine whether they are the same. (2) Studies on the regulation of gene expression in normal and neoplastic cells: In these studies we measure and compare patterns of synthesis of placental proteins in normal trophoblast, in choriocarcinoma and in non-trophoblastic tumors to determine whether similar regulatory mechanisms are operant. These experiments are performed using tissue cultures derived from trophoblasts and from tumors which synthesize placental proteins ectopically. In addition, we are using developed cell lines. In these investigations we are specifically studying the membrane glycoproteins of the placenta and their expression in cell lines derived from human neoplasms.